MRP/GST SYNERGY IN MULTIDRUG RESISTANCE

Wake Forest University Health Sciences, Winston-Salem NC

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Abstract

The mechanisms involved in detoxification of drugs and poisons are important to cancer biology. The ability of a cell or tissue to detoxify xenobiotic poisons are associated with the emergence of anti-cancer drug resistance in tumors. In normal tissues, this detoxification activity influences the outcome of exposure to carcinogens and other toxins. A long term goal of the studies proposed is to understand the mechanisms by which the drug conjugating system, glutathione (GSH) and glutathione transferase (GST) and glutathione transferase (GST), and the toxin efflux transporters, MRP1 and MRP2, operate together to confer protection from anti-cancer drugs or carcinogens. This knowledge will improve the ability to predict the responses of particular tissues and tumors to toxin exposure including the risk of developing cancer in normal tissues or the likelihood of develop drug resistance in cancer. Moreover, this knowledge can be used to device more effect ant-cancer treatment or chemopreventive strategies.